1. Field of the Invention
The present invention relates to a novel dissolution cell for solids.
This invention also relates to an apparatus for studying the kinetics of dissolution of a solid, which apparatus comprises at least one such cell.
2. Description of the Prior Art
In research and in industry, it is often necessary to determine the speed at which a soluble solid substance is dissolved by a solvent. Such a requirement is experienced, particularly, in research in pharmacology and biology. For example, in pharmacology the measurement of the speed, or rate, at which a solid substance dissolves in a solvent is necessary for determining the efficacy and the characteristics of this solid substance. Thus, the speed at which a tablet dissolves in the digestive tract influences the speed at which the active components of the tablet will enter the bloodstream of the patient (bioavailability). It is therefore necessary to measure this speed precisely in order to define both the composition and the presentation of a medicament in solid form, such that the dosage form gives the expected effect.
In industry, the measurement of the speed of dissolution of a tablet is frequently used in manufacturing control procedures.
A pharmaceutical tablet typically comprises two principal components, namely, the active principle and a binder therefor which permits shaping the tablet and imparting mechanical strength thereto. The binder also confines the active principle and releases its gradually after absorption.
The methods for studying the kinetics o dissolution of a tablet, more generally of a solid, are defined by the European Pharmacopoeia Commission in the pharmacopoeia note for 1990, paragraph V.5.4.A. entitled "Continuous flow cell method".
In particular, the pharmacopoeia note specifies the requirements for studying the kinetics of dissolution of a solid substance by the continuous flow cell method.
The apparatus described is principally a cell, made of glass or a plastic material, whose useful volume is a cylinder, and at the lower end of the cylinder a cone is attached. The cone is pierced by a hole at its tip for the supply of the solvent. A circular filter, for example made of glass microfibers, is secured to the upper end of the cylinder over the entire cross-section of the useful volume. In order to distribute the solvent uniformly over the entire cross-section of the cell, the conical section is filled with a packing, for example of spherical glass balls. After passing through the filter, the solute is removed at the top end of the cell and then directed to a sample-collecting system or directly to an analyzer.
The pharmacopoeia note specifies the dimensional characteristics of the useful volume of the cell and of the cone and recommends flushing the cell with a continuous flowstream of solvent at a flowrate measured with a precision of 5%.
In order to obtain good analytical results, it is necessary to retain all the particles of binder present in the cell, and for this purpose filters are used, the porosity of which is on the order of a few microns. Thus, this results in the phenomenon of clogging of the filter, which gives rise to an increase in the head losses of the solvent/solute circuit and consequently produces an increase in the pressure inside the cell.
In order to limit this phenomenon, it is therefore important to provide a large filtration surface. It is also sometimes necessary, in specific cases, to be able to increase the filtration surface for a given cell.
Nonetheless, this is impossible using a cell such as that described in the pharmacopoeia note, since the surface of the filter is determined by the internal cross-section of the cell.
Moreover, it is often necessary to determine with precision the parameters such as temperature, pressure, pH of the liquid medium present in the cell, it being possible for variations in these parameters to have a very strong influence on the kinetics of dissolution of the solid substance.
Also, a cell such as described above does not permit simple introduction of one or more measurement probes into the liquid medium in the cell.